Issue Archive

An Alternative Approach to Combination Vaccines

As the number of investigational and
approved vaccines continues to increase,
the frequency of vaccinations will soon
reach a practical limit. The development
of combination vaccines is a common
practice that addresses the concern of
repeated visits to the clinic by reducing
the total number of injections required
compared with administration schedules
for the monovalent vaccines. Yet, physical,
chemical, and biological interactions
among the components of combination
vaccines must be considered to
avoid detrimental effects on safety or
efficacy. For example, when the
Haemophilus influenzae type b (Hib)
vaccine was combined with diphtheria,
tetanus, and acellular pertussis vaccine,
a decrease in antibody titer for the Hib
vaccine was observed. Thus, there is a
need to develop new approaches for
delivery of multiple vaccines.

A method of protective vaccination
against multiple diseases by intradermal
administration of each antigen to physically
isolated sites is being investigated.
This method is aimed at avoiding potentially
incompatible vaccine mixtures. As
a possible alternative to combination
vaccines, specially designed microneedles
are used to inject four separate
recombinant protein vaccines for
anthrax, botulism, plague, and staphylococcal
toxic shock next to each other
just below the surface of the skin.

The delivery of multiple vaccines
intradermally was evaluated to physically
isolate each component, thus directly
preventing formulation incompatibilities
prior to administration. The physiological
fate of vaccines administered
intradermally is not known. However,
vaccination by microneedles permits verification
of the physical deposition into
the skin, while intramuscular injection
sites are inaccessible for direct observation.
Further, intradermal vaccination
using microneedles is less painful than
intramuscular injection by conventional
needles and provides an increased
immune response with a lower amount
of vaccine than that required by intramuscular
methods.

The intradermally administered vaccines
retained potent antibody responses
and were well tolerated. Based on
tracking of the adjuvant, the vaccines
were transported from the dermis to
draining lymph nodes by antigen-presenting
cells. Vaccinated primates were
completely protected from an otherwise
lethal aerosol challenge by Bacillus
anthracis spores, botulinum neurotoxin
A, or staphylococcal enterotoxin B.

The physical separation of vaccines
both in the syringe and at the site of
administration did not adversely affect
the biological activity of any component
vaccine. Further, the vaccination
method described may be scalable to
include a greater number of antigens, while avoiding the physical and chemical
incompatibilities encountered by
combining multiple vaccines together in
one product. The results demonstrate
that intradermal delivery of multiple
vaccine preparations may provide a
practical alternative to traditional combination
vaccines and complicated
administration schedules.

This work was done by Garry L. Morefield,
Ralph F. Tammariello, Bret K. Purcell,
Patricia L. Worsham, Jennifer Chapman,
Leonard A. Smith, and Robert G. Ulrich of the
Army Medical Research Institute of Infectious
Diseases; and Jason B. Alarcon and John A.
Mikszta of Becton Dickinson Tech nologies. For
more information, download the Technical
Support Package (free white paper) at
www.techbriefs.com/tsp under the Bio-Medical category. ARL-0061

This Brief includes a Technical Support Package (TSP).

An Alternative Approach to Combination Vaccines (reference ARL-0061) is currently available for download from the TSP library.

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